rs35544003
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001379180.1(ESRRB):c.144C>A(p.Ile48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,613,444 control chromosomes in the GnomAD database, including 4,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.076 ( 605 hom., cov: 33)
Exomes 𝑓: 0.063 ( 4309 hom. )
Consequence
ESRRB
NM_001379180.1 synonymous
NM_001379180.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.310
Genes affected
ESRRB (HGNC:3473): (estrogen related receptor beta) This gene encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
?
Variant 14-76439434-C-A is Benign according to our data. Variant chr14-76439434-C-A is described in ClinVar as [Benign]. Clinvar id is 45001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.31 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESRRB | NM_001379180.1 | c.144C>A | p.Ile48= | synonymous_variant | 2/7 | ENST00000644823.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESRRB | ENST00000644823.1 | c.144C>A | p.Ile48= | synonymous_variant | 2/7 | NM_001379180.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0762 AC: 11603AN: 152184Hom.: 601 Cov.: 33
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GnomAD3 exomes AF: 0.0869 AC: 21504AN: 247442Hom.: 1338 AF XY: 0.0861 AC XY: 11597AN XY: 134658
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GnomAD4 exome AF: 0.0635 AC: 92781AN: 1461142Hom.: 4309 Cov.: 36 AF XY: 0.0652 AC XY: 47392AN XY: 726870
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GnomAD4 genome ? AF: 0.0764 AC: 11633AN: 152302Hom.: 605 Cov.: 33 AF XY: 0.0799 AC XY: 5950AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ile27Ile in Exon 04 of ESRRB: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 8.1% (301/3718) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35544003). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive nonsyndromic hearing loss 35 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at